1. Field of the Invention
The present invention relates to a method of preparing calcium phosphate which is utilized as a raw material for bioceramics such as bone supplement material, an artificial tooth root, an artificial joint, bone pin, a percutaneous terminal and artificial an bone, etc. Particularly the present invention relates to a method of preparing calcium phosphate which is biologically safe and free from hemolysis, etc.
2. Description of the Related Art
Recently research and developments have been flourishing with respect to bioactive calcium phosphate which is used for bone supplement material, an artificial tooth root, etc.
There have been known such conventional methods of preparing calcium phosphate, such as a dry synthesis wherein a powdery raw material is subjected to a solid phase reaction under an elevated temperature, and a wet synthesis wherein raw material solutions and/or a raw material slurry are reacted. Any of these methods, however, has hardly been able to provide a product of high purity. Furthermore, the production of high-purity calcium phosphate by said conventional methods has resulted not only in complicated processes but also high costs.
As a method to overcome the above stated problems, a method of preparing .beta.-tricalcium phosphate (referred to as .beta.-TCP hereafter) powder through a so-called wet attrition synthesis utilizing a mechanochemical reaction, has been disclosed in e.g. U.S. Pat. No. 4,717,556, which is a method capable of producing high-purity calcium phosphate in a simple and economical way.
Some of the embodiments of the above mentioned U.S. Pat. No. 4,717,556 have disclosed two cases of preparation of .beta.-TCP in which prepared .beta.-TCP has an atomic ratio of calcium atom relative to a phosphorus atom (referred to as Ca/P atomic ratio hereafter) of 1.5 or 1.67, respectively. Also there have been descriptions that said methods can provide powdery .beta.-TCP having a large specific surface area.
However, in said U.S. Pat. No. 4,717,556 the biological safety of thus synthesized .beta.-TCP and hydroxylapatite (HAP) has not been examined sufficiently. Namely U.S. Pat. No. 4,717,556 as mentioned above describes that by adjusting the Ca/P atomic ratio to 1.5 of the raw materials and a calcination temperature to 750.degree. C. the calcium phosphate can be produced in an economical and industrially practicable way. But there is also a description that the calcination time depends on an X-ray diffraction strength of dried powder of .beta.-TCP hydrate of pre-calcination. Also there is stated that the crystallinity of powder of dried .beta.-TCP of post-calcination changes depending on the calcination time. More specifically, in said U.S. Pat. No. 4,717,556 there is disclosed that when dry powder of .beta.-TCP hydrate is calcinated at a temperature of 750.degree. C. or more, the diffraction strength will be increased. Furthermore, it is generally known that, when the calcination temperature is 1,150.degree. C. or more, a transition from .beta.-TCP to .alpha.-TCP may occur resulting in a change of crystallinity of the obtained .beta.-TCP.
As stated above, there are instances where high purity powdery calcium phosphate having a desired crystallinity cannot be produced by the mechanochemical method in accordance with said U.S. Pat. No. 4,717,556. The purity of the powder depends on the calcination time and temperature. Furthermore the powdery calcium phosphate thus obtained is apt to contain non-reacted matter like Ca(OH).sub.2 etc., which will cause hemolysis. Consequently, the produced calcium phosphate powder may show a hemolytic property occasionally.
Calcium phosphate type ceramics have been known to have not only hemolysis but also an antigenicity.
Still further, ceramics such as TCP and HAP, etc., have been known to show a cytotoxicity. An intensity of the cytotoxicity is confirmed to be different depending on, for instance, a kind of preparation method (e.g., dry or wet method) and calcination temperature.
As described above, calcium phosphate prepared in accordance with said U.S. Pat. No. 4,717,556 may cause hemolysis, antigenicity and cytotoxicity, which have drawbacks in the view point of biological safety. Thus it is not preferable to use such calcium phosphate as a biomaterial.